The ocular surface epithelium undergoes continuous, dynamic turnover, which is part of a normal shedding process. This turnover is increased in subjects suffering from various forms of nucleic acid-related eye disease, such as dry eye disease (DED). Superficial corneal cells are shed into the precorneal tear film. The corneal epithelial cell shedding process, or desquamation, is regulated by apoptotic mechanisms. Dead and dying cells release nucleic acid, a type of damage-associated molecular pattern molecule, which can stimulate the innate immune system and link it to adaptive immune system. Extracellular DNA strands, for example, have been reported in corneal filaments, which are frequently present on the corneas of patients with DED. Desquamated cells in the precorneal tear film are a potential source of extracellular DNA. Tear fluid contains several neutrophil extracellular trap (NET) components. Neutrophils undergo a low level of recruitment on the ocular surface, and numerous neutrophils are present in the tear film during ocular surface inflammation, which has a prominent role in symptom development and amplification. Neutrophil elastase and histone proteins have also been reported in tear fluid. These reports document the presence of extracellular DNA, histones, neutrophils, neutrophil elastase, and nucleases in tear fluid and perhaps suggest mechanisms exist for the continual production and clearance of extracellular DNA in tear film.
Extracellular DNA in tear film, such as ocular biofilm and mucoid film, may play a role in the pathology associated with nucleic acid-related eye disease. Nucleic acid-related eye diseases that may be associated with the formation of ocular mucoid films and/or biofilms present potentially disabling conditions, which adversely impact the vision-related quality of life. They can lead to ocular discomfort and/or deterioration in visual performance, such as reading speed and contrast sensitivity.
Despite the high incidence of nucleic acid-related eye diseases, there is currently no consistently effective treatment for these conditions. Because hyperosmolarity and inflammation have traditionally been thought as central reasons for dry eye disease, for example, current treatments focus on the use of eye-lid hygiene, topical antibiotics, oral tetracyclines, anti-inflammatories and/or corticosteroids. Such treatments are often ineffective or variably effective. As such there is a need for new therapeutic modalities to treat nucleic acid-related eye diseases, such as DED, that can result from the production/formation of nucleic acid in conjunction with ocular mucoid films and/or biofilms, for example.